1. Field of Invention
This invention relates to the area of human vision correction, specifically relating to the use of short pulse laser beams to precisely remove ocular tissue to change the refractive power of the human eye.
2. Background of the Invention
The invention relates to procedures and apparatus for performing refractive surgery in the central aspect of the cornea to correct refractive errors of the eye. The invention uses ultrashort pulsed laser to perform all aspects of the corneal surgery, including the creation of incisions and the direct ablation of corneal tissue. In particular, the invention replaces the use of UV ablating lasers in procedures such as laser-assisted in-situ keratomileusis (LASIK) with an ultrashort pulsed laser.
Corneal Refractive Laser Surgery
Modern corneal refractive surgery techniques draw upon the original work of Dr. Jose I. Barraquer. Briefly, in 1958, Dr. Barraquer first developed keratomileusis techniques based on the removal of a lenticular volume of corneal tissue by mechanical means. In 1990, Pallikaris et al reported the use of an excimer laser was used to ablate the lenticular volume in the first LASIK cases. The development of LASIK and related procedures is described in Section Three, pages 147-222 of the text book “Refractive Surgery”, 2nd edition, 2007, edited by Dimitri Azar.
In the development of corneal refractive correction with lasers, direct ablation of the corneal anterior surface with an ultraviolet (UV) laser was used. An early example is the method of L'Esperance, Jr. in U.S. Pat. No. 4,665,913. The UV laser was typically an excimer laser. The laser ablation was performed with repeated patterns of laser pulses arranged in a specific geometry. The pattern of ablating pulses produced a change in the corneal shape and therefore the refractive power of the eye. This procedure is called photorefractive keratectomy (PRK). The limits of this approach include the fact that direct ablation of the anterior layers of the cornea, including Bowman's layer and the anterior corneal stroma, produce tissue remodeling and a wound healing response that limit and degrade the optical outcome.
Laser-assisted in situ keratomileusis (LASIK) was developed to overcome the limits of PRK. In U.S. Pat. No. 4,840,175, Peyman first detailed the method which later came to be known as LASIK. In LASIK, a mechanical blade first makes a corneal flap cut. Subsequent manual lifting of the flap exposes the inner corneal tissue, referred to as the corneal stroma. The stroma is then subjected to an ablating UV laser beam. The ablating UV laser beam removes a volume of corneal tissue according to a specific mathematical prescription for producing the desired curvature change. In a later development, Munnerlyn in U.S. Pat. No. 5,163,934, employed a difference of sphere formulation to determine the lenticular volume to be removed for a treatment of myopia. The success of LASIK was swift, but used a two-stage, two-instrument procedure. A significant limitation of LASIK is the reliability, precision and quality of the blade cuts to produce the corneal flap. A second limitation is the requirement that nomograms be developed to compensate for the biological response to ablation, and to the geometry-dependent efficiency of UV laser ablation of the corneal stroma. A third limitation is that the low spatial frequency of the ablation patterns realizable with excimer laser ablation. That is, the lateral size of the ablation compared to the ablation depth of a single pulse makes it difficult to stack pulses in a way that allows for arbitrary ablation profiles. Typically, the profiles in LASIK and PRK vary slowly, which from a visual outcomes point of view is rather good. However, if a small amount of tissue is to be removed, such as may occur in a complication of refractive surgery, of if a higher order aberration is to be corrected by removal of a volume of tissue having relatively steeply angled features, large spot excimer ablation may not be efficacious.
LASIK and PRK are performed using a UV laser, typically an excimer laser, to perform the ablative part of the procedure. Examples of excimer laser keratomes include the Visx Star S4 from Abbott Medical Optics, Santa Ana, Calif.; the Technolas 217A from Technolas Perfect Vision GmbH, Munich, Germany; or the LADARVision 4000 and the Allegretto Wave from Alcon Laboratories, Inc., Fort Worth, Tex.
An alternative to LASIK and PRK was suggested and developed by Bille and Juhasz in U.S. Pat. No. 4,907,586 and further refined in U.S. Pat. No. 5,993,438. In this method, a focused ultrashort pulsed laser beam is scanned inside the cornea to create a defined volume of vaporized tissue consisting of many individual small-scale photodisruptions. The volume of tissue would be vaporized and ultimately resorbed by the surrounding corneal tissue. The resulting new corneal shape would produce the desired refractive correction. This approach is referred to as intrastromal or intrastromal ablation. A picosecond laser instrument by Intelligent Surgical Lasers was developed for this procedure. Limitations to the method were several. One limitation is the relatively large volumes of vapor produced in the stroma which limit the amount of tissue that can be destroyed or removed. A second limitation is that the vaporization of tissue for the purpose of altering the shape of the cornea through relaxation of the overlying anterior surface survace is limited by the natural stiffness of the corneal membranes. The native stiffness of the corneal limits the size of the refractive change that can be produced in this method.
Ultrashort pulsed lasers were commercially introduced into corneal refractive surgery with the development of femtosecond laser flap cutter instruments. Mourou et al in U.S. Pat. No. 5,656,186 described a method for using femtosecond pulses which allows for a more deterministic and precise machining of materials, including biological tissues, relative to picosecond lasers. Femtosecond lasers assist in the LASIK procedure by replacing the mechanical microkeratomes used in the corneal flap cutting step. The corneal cuts produced are precise and can have arbitrary three dimensional shapes, surpassing what can be achieved with mechanical blades. A limitation of the approach is that the actual refractive correction still requires the use of a second laser, namely an excimer laser.
Incisional ultrashort pulsed laser keratomes generate, process and deliver a train of scanned, tightly focused ultrashort laser pulses onto or into the volume of a fixed or immobilized cornea. The laser sources used generally employ a chirped pulse amplification technique with a large bandwidth lasing medium, such as Ti:S, Nd:glass or Yb:fiber. Typically, the laser pulses energies range from 0.1-10 microJoules, the pulse widths are <1 picosecond, the beam quality is near-diffraction-limited, and the wavelength falls between the NIR and the visible (typ 800-1100 nm) so as to avoid significant heating of water or tissue by linear absorption in the corneal tissue. Commercially available instruments operate at laser repetitions between 30 kHz and 2 MHz, depending on the design, model and manufacturer. A high speed 2D beam scanner in combination with a high numerical aperture focusing objective allows for the precise placement of tightly focused spots throughout the volume of the human cornea. In a typical femtosecond laser keratome the cornea is fixed with respect to the keratome optical axis and the cornea is lightly held in place and applanated by a contact glass and suction ring.
A purely incisional approach to refractive surgery using a single ultrashort pulsed laser instrument was taught by Juhasz in U.S. Pat. No. 6,110,166. In this approach, multiple laser cuts define a disk-shaped block of corneal stromal tissue underlying a laser-cut flap. The flap is manually lifted and the disk-shaped corneal plug or disk is manually removed. When the flap is replaced, the change in the corneal shape resulting from the missing corneal tissue lenticle produces an appropriate change in refractive power. This change can be accomplished without the need for an ablation step by a UV laser. The approach was similar to an earlier refractive surgery performed with a mechanical blade. The mechanical approach was called automated lamellar keratoplasty or ALK, introduced by Ruiz et al in U.S. Pat. No. 5,133,726. A limitation of both the ALK and the femtosecond laser keratomileusis procedure was the relatively poor refractive outcomes associated with removing a disk of planar geometry, rather than a disk of the ideal lenticule shape according to Munnerlyn and others.
An improved approach over Juhasz is found in United States Patent Application No. 20080319428 of Weichmann et al. The volume of the stromal disk of tissue to be laser cut and manually removed have anterior and posterior surfaces having curvatures rather than being planar. The invention advantageously allows for the realization of ideal shapes of the tissue to be removed. A limitation is that the tissue to be removed manual after cutting may tear or fragment, and cannot easily be removed by laser or by other means. A related limitation is that the axial thickness of the tissue to be removed may be associated with a minimum thickness. Some refractive corrections may require cutting a thin cross section volume of tissue. If the tissue is too thin, it may be too friable. This aspect places limitations on the ranges of potential refractive corrections achievable by this method. A further limitation is that the gas produced in the first portion of tissue vaporized may produce movement or changes in the cornea that interfere with the vaporization of subsequent portion of tissue.
U.S. Pat. No. 4,907,586 also contains a method of corneal refractive surgery in which the optical properties of the cornea are directly altered by a scanning ultrashort pulsed laser. In this method, index of refractive of the targeted volume produces the desired refractive correction. A limitation of this method is the size and stability of the refractive changes to the cornea.
Direct Ablation of Tissue
In LASIK, excimer lasers directly photoablate the corneal tissue they impinge upon. The controlled ablation of corneal stroma tissue produces the desired shape change.
Ultrashort pulsed lasers, such as femtosecond lasers, are widely used to incise cornea through the mechanism of photodisruption. Present clinical use of ultrashort pulsed lasers in the eye employs photodisruption and not the true ablation associated with excimer lasers in cornea. That is, ultrashort pulsed lasers are used to cut cornea rather than ablate it. This is quite sensible in that the natural advantage of using an ultrashort pulsed laser in transparent tissue is that highly localized, small photodisruption events can be arranged to create cut planes or surfaces.
Some confusion exists in the art about the term “ablation”. When ultrashort pulsed lasers are used in ophthalmic surgery, the laser-tissue interaction is generally the creation of incisions through the cumulative effect of many individual photodisruption events. In physical processes, ablation refers to the physical processes, such as melting and vaporizing, that result in the ejection of material from the ablation site. The confusion is likely due to the use of the term ablation in medicine. In medical usage, ablation means the localized destruction of tissue, but not usually the physical ejection of tissue through melting or vaporization.
An aspect of my invention is physical ablation of corneal and ocular tissue with ultrashort pulsed lasers. I therefore differentiate between the usage of the term “ablation” in the prior art of ultrashort pulse lasers and the meaning of term is used in my invention. Here, when I use the term “ablation” with ultrashort pulsed lasers, I mean the physical removal of tissue resulting from the laser interaction, whether as a result of a photodisruption event or by some other interaction. Typically I use the term “ablative mode” in this context. When referring to the creation of cuts or incisions, I will use the term “incisional mode”.
Two examples of this confusion in terminology are found in Zhang et al (“Morphologic and histopathologic changes in the rabbit cornea produced by femtosecond laser-assisted multilayer intrastromal ablation”, IOVS, May 2009, Vol. 50, No. 5.) and Wang et al (“In-vivo intratissue ablation by nanojoule near-infrared femtosecond laser pulses”, Cell Tissue Res 2007, Vol. 328:515-520) In the first reference, the authors use the term ablation, but the actual laser-tissue interaction in the cornea was intrastromal photodisruption, which was arranged to create multiple dissection planes inside the cornea. In the second reference, the authors also use the term ablation, but again the laser-tissue interaction was the photodisruptive destruction of corneal tissue on a small scale by nanoJoule laser pulses. True ablation was not occurring in either case.
Certainly ultrashort pulse laser ablation is used in a wide variety of material processing applications. However, the use of ultrashort pulse laser ablation of exposed cornea surfaces for clinical procedures is limited by several factors. An important limitation is the limits placed on input average power and input pulse energy to the cornea by safety considerations associated with non-target tissues such as the retina. A second limitation is the requirements placed on the positioning of a tightly focused laser spot at or near the target surface. This limitation in consideration of available practical ultrashort pulse laser sources results in micron precision in the positioning of the laser focus with respect to the target tissue surface. It is a further limitation that when positioning registration of a focused ultrashort laser beam with respect to a target tissue surface is achieved, very small motion associated with the involuntary movements of the eye may interrupt tissue ablation before a meaningful volume of tissue can be ablated.
Posterior Flap Ablation
The stromal surface targeted for laser ablation is created by manually lifting and reflecting the anterior flap of tissue produced by blade or ultrashort laser cutting. It is generally advantageous to target the exposed stromal bed for excimer laser ablation. In some excimer laser treatments, it may be advantageous to target the posterior surface of the lifted flap instead of the stromal bed. For example, Maldonado retreated LASIK patients by lifting a flap, manually marking the corneal flap anterior surface and manually directing an excimer ablation pattern with the laser keratome eye tracking system turned off (“Undersurface ablation of the flap for laser in situ keratomileusis retreatment”, Ophthalmology Vol. 109, No. 8, August 2002). Maldonado marked the posterior flap surface with Gentian violent ink and a hand instrument referred to as a para-radial marker. He relied on visualizing the marked pattern and manually orienting the laser ablation pattern. He noted that a major challenge was stabilizing the eye and flap, and used hand instruments to stabilize the flap, relying on the reflected flap to lie on the eye anterior surface for the ablation. A limitation of the approach of Maldonado is the poor stability of the reflected flap tissue subject to laser radiation. A secondary limitation is the uncertainty in the positioning of the flap posterior surface. These limitations are less important in the case of excimer laser pulse interaction, but are important in the potential use of tightly focused ultrashort pulses, a feature of my invention.
Eye Tracking and Corneal Marking
The corneal is usually marked for refractive surgery. In LASIK or other laser refractive surgery, hand instruments inked with Gentian violet or another biocompatible dye are used to demarcate the corneal center, the optical zone or other orientation information to facilitate the positioning and placement of both the flap cutting keratome and the excimer laser keratome instruments. Marking is typically done by hand or with hand instruments. Marking is used to center and orient the placement of microkeratomes or the placement of excimer laser treatments. A typical hand instrument for marking the cornea in preparation for laser refractive surgery is taught by Kritzinger in U.S. Pat. No. 5,752,967. Further examples of marking instruments may be found in the extensive catalog of manual instruments available from Katena Products, Inc, Denville, N.J.
The biocompatible inks used for corneal marking can be oil-based or water-based inks. Water-based inks—typically a formulation of Gentian violet dye—do not bind strongly to the cornea. In fact, the water-based ink washes off quite easily, and tears, blinking or eye drops can easily fade the markings before the laser procedure. For this reason, oil-based inks are often preferred. According to Ide et al (“Effect of marking pens on femtosecond laser-assisted flap creation”, J Cataract Refract Surg 2009; 35:1087-1090), a limitation of oil-based inks is the tendency for the inks to interfere with the transmission of ultrashort or femtosecond laser beams used to create corneal flaps. A further limitation of oil-based inks is the difficulty of removing the inks after the laser procedure is complete.
Laser surgery of the cornea requires precise placement of the laser pulses with respect to the location of the tissue surfaces. Voluntary and involuntary movement of the eye relative to the laser beam optical axis may prevent the desired placement of pulses. Saccadic and slower drifts of the eye may be mitigated by instructing patients to fix their gaze on a distant object or image. The human eye during directed fixation of the gaze exhibits three types of involuntary motion: tremor, microsaccades, and drifts (Physiology of the Eye, Dawson ed., page 663). These movements occur on several time and amplitude scales. Additionally, voluntary or reflexive motion may occur depending on the patient's mental state and environmental stimuli. In corneal refractive laser surgery a need exists to compensate for these movements. These approaches are useful, but insufficient for precision laser surgery of the cornea by excimer lasers, and less useful in ultrashort pulsed laser surgery of the cornea.
A mechanical means to restrain the subject eye may also be used. Restraining the eye generally requires pressure or low vacuum forces to be applied to some part of the anterior portion of the eye globe. The application of such forces can lead to discomfort, injury and surgical complications. Additionally, restraining the eye is not sufficient for all eye motion.
A well-established feature of LASIK and other laser-based corneal refractive surgeries is the detection of, and compensation for, eye movements through the use of eye-tracking technology. Typically, eye trackers employ multiple digital cameras to image high contrast anatomic structures, such as the iris or the pupil edge. Software and firmware processing of the images then produce image registration information that is used to track the motion of defined features. An early example of eye tracking for PRK was taught by Smith in U.S. Pat. No. 5,350,374. Eye tracking may be used passively or actively. Passive eye tracking halts laser treatment when the eye motion ranges beyond an acceptable limit. Active eye tracking continuously compensates for eye motion by re-directing the beam position and angle to match eye movement. A limitation of eye tracking technology with respect to potential use in ultrashort pulsed laser treatments is that the highest speed eye tracking technology available works in the kHz range, or has an equivalent bandwidth. Femtosecond lasers used to incise cornea now operate in the 100's of kHz range. The present invention optimally uses laser sources of pulse repetition rate above 1 MHz pulse repetition rate. A limitation of the existing eye tracking art is that the speed of eye trackers does not match the high repetition rates of ultrashort pulsed lasers that can perform clinically relevant ablation rates in an unrestrained cornea.
An alternative approach is the use of radar technology as in the Ladarvision 4000, Alcon, Inc.
In ultrashort pulse corneal surgery, eye tracking is not performed. The distance tolerances for positioning the focused laser beam and the scanning path of the focus with respect to the corneal surface are high, and are typically on the order of a few microns. The invention taught by Juhasz in U.S. Pat. No. 6,254,595 uses an applanating optic in combination with a “skirt” that uses suction to apply a ring of suction force to the eye. This approach, essentially universal with ultrashort pulsed laser keratomes for corneal surgery, functions well for the incisional modality used presently by all commercial instruments. Applanating optics may be planar, as in the invention of Juhasz, or they may have a curved surface conforming to the shape of the cornea. These solutions work well for ultrashort pulsed laser incision cutting, because there is no need to allow material to be ejected from the target surfaces. A limitation of applanating devices is that direct ablation cannot be done at the same time. A means of placing tightly focused ultrashort pulsed laser pulses at targeted surface(s), with the targeted surface(s) unobstructed, is needed to enable the ablation modality of the present invention.
Bille et al teach the use of laser-produced bubbles on the surface of the cornea to serve as tracking features for a laser-based tracking system in U.S. Pat. No. 4,848,340. One limitation of this invention is the low contrast that a surface ablation feature on the cornea presents. A second limitation is the undesirability of introducing additional injuries or lesions to the surface of the cornea.
In U.S. Pat. No. 6,579,282, Bille et al teach the placement of bubbles created inside the corneal stroma by laser photoablation, with the bubbles serving as guide features for image-based eye tracking systems. The bubble features for eye tracking are created rapidly by a scanning laser, and may be created by an ultrashort pulsed laser. A limitation of this approach is the low contrast bubbles may present to eye tracking systems. A second limitation is that laser-generated bubbles in stroma dissolve and are resorbed in the corneal tissue over time. A third limitation is the well-known phenomenon from ultrashort pulsed laser corneal surgery in which bubbles created by laser vaporization in the corneal stroma move along lamellar planes in unpredictable ways.
3. Objects and Advantages
Accordingly, in addition to the objects and advantages of the apparatus and methods described in my above patent, several objects and advantages of the present invention are:                a) to provide a means of inducing a refractive change in the human eye by direct removal of corneal tissue with ultrashort pulsed laser ablation;        b) to provide a means for ablating stromal tissue on the posterior surface of an exposed corneal flap with an ultrashort pulsed laser;        c) to provide a means of allowing the use of high average power and high pulse energy ultrashort pulsed laser beams to ablate ocular tissue that exceed safe limits when used on an exposed corneal stromal bed as in LASIK or related treatments;        d) to provide a means of producing ablation profiles of ocular tissue of high spatial modulation;        e) to provide a means of ablating and thereby removing tissue with small lateral dimensions as in an adhesion or tag of corneal tissue;        f) to provide a means of removing sections of corneal tissue of thickness smaller or more friable than can be safely removed and cut by incisional means;        g) to provide a means of ablating ocular tissue with high pulse rate ultrashort pulsed lasers that allows for relaxed positional tolerances between target tissue and ablating beam;        h) to provide a means of ablating ocular tissue with high pulse rate ultrashort pulsed lasers using an imaging eye tracking system to compensate for involuntary motion of the eye;        i) to provide a means of incising or ablating ocular tissue with ultrashort pulsed lasers without the need for an applanating optic in contact with the cornea;        j) to provide a means of creating high contrast fiduciary marks in cornea for use with an image-based eye tracking system;        k) to provide a means of creating fiduciary mark features in human cornea with ultrashort pulsed laser incisions having sufficiently small width so as to avoid interfering with visual acuity of the patient;        l) to provide a means of creating fiduciary mark features in human cornea with ultrashort pulsed laser incisions which can be selectively impregnated with water-based dyes;        
One advantage of the present invention is that a single laser platform may be used to perform corneal refractive surgery, eliminating the need for two separate and expensive laser systems. A further advantage is that the invention may be used to create incisions and to directly ablate tissue to create a refractive effect, allowing a single instrument to perform many of the procedures presently performed by various laser and non-laser keratome instruments. A further advantage is that the invention requires less direct contact with the eye relative to other ultrashort laser keratomes, offering the possibility of vision correction procedures that are less invasive than at present. In particular, some incisional procedures may be performed without the need for an applanating optic in contact with the cornea. Such minimal touch surgical procedures reduce the risk of infection, allow for greater patient comfort, and are associated with lower complication rates.
Further objects and advantages will become apparent from a consideration of the drawings and ensuing description.